Abstract 5396: DNA damage repair gene mutations predict the efficacy of immunization combined with platinum chemotherapy in advanced non-small cell lung cancer: A retrospective cohort study
Authors: Zhiwe Xiao, Lingling Sun, Yating Zheng, Hanrui Chen, Xinting Zheng, Jiamin Luo, Chuying Gu, Ruiting Lin, Xue Hu, Mengli Huang, Lizhu Lin
Journal: Cancer Research (2022)

Abstract Purpose: DNA damage repair (DDR) mutations are known to predict response to platinum-based chemotherapy in multiple solid tumors, as well as immunotherapy in non-small cell lung cancer (NSCLC). However, the predictive value of DDR in immunization combined with platinum chemotherapy remains unclear. Methods: We retrospectively collected information from 495 patients with advanced NSCLC whose tumors were analyzed using next-generation sequencing (NGS) and analyzed the characteristics of DDR mutations. Among them, 64 patients with NSCLC who received platinum chemotherapy and 37 patients who received immunotherapy combined with platinum chemotherapy were included in the prognostic analysis. Results: The DDR genes was commonly mutated in Chinese NSCLC population (242/495, 48.89%). In Chinese NSCLC cohort, DDR mutations showed a strong association with high tumor mutational burden (TMB-H) (DDR mutant vs DDR wild-type: 7.26 muts/Mb vs 5.15 muts/Mb, P=0.001) and higher rates of strong PD-L1 (TPS≥50%) positivity (DDR mutant vs DDR wild-type: 28.74% vs 20.69). Sixty-four advanced NSCLC patients treated with platinum-based chemotherapy were analyzed, the ORRs were 16% for the patients with DDR mutations (DDRmut) and 2.70% for the DDR wild-type (DDRwt) subgroup (P&amp;lt;0.05), and the DCRs were 88% for the DDRmut group and 48.64% for the DDRwt group (P&amp;lt;0.05). The DDRmut patients had significantly improved median PFS than the DDRwt group (7.07 months vs 4.27 months, hazard ratio (HR) =0.57, 95%CI 0.33−0.97, P= 0.0303). Median OS was also significantly better among the DDRmut patients than in the DDRwt group (29.93 vs 20.7 months, HR=0.49, 95%CI 0.25−0.97, P= 0.0359). Moreover, in thirty-Seven advanced NSCLC patients treated with immunization combined with platinum chemotherapy, the ORRs were 45% for the patients with DDR mutations (DDRmut) and 11.76% for the DDR wild-type (DDRwt) subgroup (P&amp;lt;0.05), and the DCRs were 95% for the DDRmut group and 70.59% for the DDRwt group (P&amp;lt;0.05). The DDRmut patients had significantly improved median PFS than the DDRwt group (16.83 months vs 5.83 months, hazard ratio (HR) =0.34, 95%CI 0.12−0.973, P= 0.0079). For patients in the DDRmut group, PFS receiving immunization combined with platinum chemotherapy was significantly better than those receiving platinum-based chemotherapy (16.83 months vs 7.07 months, hazard ratio (HR) =0.48, 95%CI 0.24−0.97, P= 0.046). However, for patients in the DDRwt group, there was no significant difference in PFS between those who received immunization combined with platinum chemotherapy and those who received platinum-based chemotherapy (5.8 months vs 4.2 months, hazard ratio (HR) =0.76, 95%CI 0.394−1.495, P= 0.491). Conclusions: DDR mutations may serve as a positive predictor of immunization combined with platinum chemotherapy in patients with advanced NSCLC. Citation Format: Zhiwe Xiao, Lingling Sun, Yating Zheng, Hanrui Chen, Xinting Zheng, Jiamin Luo, Chuying Gu, Ruiting Lin, Xue Hu, Mengli Huang, Lizhu Lin. DNA damage repair gene mutations predict the efficacy of immunization combined with platinum chemotherapy in advanced non-small cell lung cancer: A retrospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5396.